Drug & Food Interactions
- Drug Interactions
- Food Interactions
The risk of bleeding is the main complication associated with coumarin anticoagulants. It is greatly influenced by the intensity of anticoagulant therapy, underlying clinical disorders of the patient and by the concomitant use of other drugs. Drugs administered in combination with acenocoumarol may have mild to fatal effects on the diseased patient.
Although pharmacodynamic interactions are identical for the two coumarin derivatives viz. warfarin and acenocoumarol, this is not the case for all pharmacokinetic interactions; as acenocoumarol, unlike warfarin, is not metabolized by CYP3A4. However, as the CYP2C9 enzyme appears to be less important for the clearance of acenocoumarol than for the clearance of warfarin, acenocoumarol may be less sensitive than warfarin. Consequently, the outcome of a drug interaction for acenocoumarol and warfarin may also differ. Some drugs may diminish the effect of acenocoumarol while several others may pose as fatal combinations. Major interactions are observed with substrates of CYP1A2 and 2C9 while minor ones with substrates of 2C19 isozymes.19,20
Drugs with a criticality index ≥ 20 exhibit highest risk of interaction with acenocoumarol, while ≥ 60 pose a high bleeding risk
INN | Criticality index |
---|---|
Amiodarone | 640 |
Acetylsalicylic acid | 600 |
Esomeprazole | 400 |
Clopidogrel | 240 |
Paracetamol | 80 |
Fluvastatin | 80 |
Celecoxib | 80 |
Fluvoxamine | 64 |
Leflunomide | 64 |
Ciprofloxacin | 60 |
Escitalopram | 40 |
Diclofenac | 40 |
Omeprazole | 40 |
Metronidazole | 30 |
Clarithromycin | 24 |
Simvastatin | 24 |
Econazole | 24 |
Prednisone | 20 |
Fluconazole | 20 |
Valproic acid | 20 |
Ibuprofen | 20 |
Lysine acetylsalicylate | 20 |
Imatinib | 20 |
Miconazole | 20 |
Pantoprazole | 20 |
Voriconazole | 20 |
Etodolac | 20 |
Ketorolac | 20 |
Criticality index based on multiplication of three scores viz. mechanism of interaction, association with supratherapeutic INR and association in bleeding.
INN, international non-proprietary name.
Mode of action (MOA) of drugs interacting with acenocoumarol
Drugs classified based on mode of action | Interaction | Drugs |
---|---|---|
CYP1A2 inducers | Decrease the effects of acenocoumarol | Aminoglutethimide, Carbamazepine, Phenobarbital, Rifampicin |
CYP1A2 inhibitors | Increase the effects of acenocoumarol | Ciprofloxacin, Fluvoxamine, Ketoconazole, Norfloxacin, Ofloxacin, Rofecoxib |
CYP2C9 inducers | Decrease the effects of acenocoumarol | Carbamazepine, Phenobarbital, Phenytoin, Rifampicin, Rifapentine Secobarbital |
CYP2C9 inhibitors | Increase the effects of acenocoumarol | Delavirdine, Fluconazole, Gemfibrozil, Ketoconazole, Nicardipine, NSAIDs, Pioglitazone, sulphonamides |
NSAIDs, nonsteroidal anti-inflammatory drugs.
List of top 10 drugs potentially interacting with acenocoumarol and their concomitant effects
Drug | Effect |
---|---|
Paracetamol (pain killer) | ↑ INR |
Acetylsalicylic acid (antiplatelet agent) | ↑ INR |
Prednisone (corticosteroid) | ↑ INR |
Tramadol (opoid pain killer) | ↑ INR |
Ceftriaxone (antibiotic) | ↑ INR |
Amlodipine (calcium channel blocker) | ↑ INR |
Clopidogrel (antiplatelet agent) | ↑ INR |
Pravastatin (statin/ anti-cholesterol agent) | ↑ INR |
Ciprofloxacin (antibiotic) | ↑ INR |
Amiodarone (antiarrhythmic) | ↑ INR |
INR, international normalized ratio.
Drugs interacting with acenocoumarol and altering international normalized ratio (INR) values
Supratherapeutic INR | Fluctuation of INR | Subtherapeutic INR |
---|---|---|
Amiodarone | Fluconazole | Carbamazepine |
Acetaminophen | Amiodarone | Phenytoin |
Acetylsalicylic acid | Rifampicin | |
Clopidogrel | ||
Esomeprazole | ||
Simvastatin | ||
Amoxicillin | ||
Clavulanic acid | ||
Ceftriaxone | ||
Fluconazole | ||
Voriconazole |
Interactions of Acenocoumarol with other drugs
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Amiodarone21 | ↑ or ↓ INR Moderate to severe |
Inhibition of CYP2C9, CYP2C19 and/or CYP1A2, reduced clearance of acenocoumarol increased risk of bleeding | Monitor INR and drug dosage, increase/ decrease in amiodarone dose may be advisable |
Tamoxifen (anti-cancer drug) | ↑ INR Major | Unknown mechanism, potentiates anticoagulation, decreases removal of acenocoumarol from blood | Warning, monitor INR for overcoagulation and bleeding episodes fatal combination, contraindicated |
Acetylcarnitine | ↑ INR Major | Increases effectiveness of acenocoumarol | Warning, monitor INR for overcoagulation and bleeding episodes, fatal combination, contraindicated |
Sitaxentan (for treatment of PAH) | Stable INR | No observed interaction | The combination is clinically manageable and well tolerated |
Nateglinide (anti-diabetic drug)22 | Stable INR | No observed interaction | May be considered for prescription as an alternative therapy |
Tamsulosin (for treatment of BPH)23 | Stable INR | No observed interaction | May be prescribed as combination therapy |
BPH, benign prostatic hyperplasia; INR, international normalized ratio; PAH, pulmonary hypertension.
Patients receiving anticoagulation therapy often require pharmaco-therapy for coexisting conditions such as hyperlipidemia. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are the most commonly prescribed class of drugs for treatment of hyperlipidemia and are recommended by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. However, several statins exhibit a strong affinity for the cytochrome P450 enzymes and inhibit its action. Hence it is likely for these drugs to have an effect on the anticoagulation efficiency of acenocoumarol. The administration of acenocoumarol along with statins possibly leads to delay in metabolism of the anticoagulant which in turn leads to enhanced anticoagulation.
Interaction of Acenocoumarol with statins
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Simvastatin (≥20 mg) | ↑ INR Severe | Delays acenocoumarol metabolism (by cytochrome P450 inhibition), potentiates anticoagulant effect | Monitor INR closely during initiation and withdrawal of therapy, may cause bleeding, consider using alternate statin therapy |
Fluvastatin | ↑ INR Severe | Delays acenocoumarol metabolism (by cytochrome P450 inhibition), potentiates anticoagulant effect | Monitor INR closely during initiation and withdrawal of therapy, may cause bleeding, consider using alternate statin therapy |
Pravastatin | ↑ INR Severe | Anticipated onset: 2-3 weeks from initiation of therapy | Monitor INR closely during initiation and withdrawal of therapy, may cause bleeding, consider using alternate statin therapy |
Lovastatin | ↑ INR Moderate | Anticipated onset: 2-3 weeks from initiation of therapy | Monitor INR closely during initiation and withdrawal of therapy, may cause bleeding, consider using alternate statin therapy |
Rosuvastatin | ↑ INR Major | Use with caution, monitor INR closely during initiation and withdrawal of therapy, may cause bleeding, empirical reduction in acenocoumarol dose may be needed | |
Atorvastatin | INR Stable | No drug interaction reported | Recommended as statin therapy along with acenocoumarol |
INR, international normalized ratio.
Drug interaction is a cause of overanticoagulation and of predominant concern in case of antibacterial drugs. Increased monitoring of INR values is warranted to prevent overanticoagulation and potential bleeding complications.
Azole antifungal drugs appear at high risk to clinically interact with acenocoumarol via a pharmacokinetic mechanism. These drug-drug interactions (DDIs) (inhibition of CYP2C9 and CYP2C19) are frequently reported and well described.
Interactions of Acenocoumarol with antibacterial, antiviral and antifungal drugs
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Antibacterial and Antiviral Drugs | |||
Amoxicillin | ↑ INR Major | High risk of bleeding | Use with caution, monitor INR closely when starting or stopping therapy, bleeding may occur, empiric reduction in acenocoumarol dose may be needed |
Azithromycin | ↑ INR Moderate to severe |
Increases anticoagulation effect by increasing serum concentration of acenocoumarol | Monitor INR closely when starting or stopping therapy, increase in anticoagulation may increase bleeding risk |
Clarithromycin | ↑ INR Moderate to severe |
A well known CYP3A4 inhibitior, interaction with acenocoumarol unknown | Monitor INR closely when starting or stopping Clarithromycin |
Cephalosporin (e.g. Cefamendole, Ceftriaxone, Cefotetan, Cefonicid) | ↑ INR Moderate to severe |
Potentiates anticoagulation | Monitor INR closely when starting or stopping therapy, risk of bleeding increases at high dose |
Erythromycin | ↑ INR Moderate to severe |
Potentiates anticoagulation | Monitor INR closely when starting or stopping therapy, risk of bleeding increases at high dose |
Chloramphenicol | ↑ INR Moderate to severe |
Potentiates anticoagulation even with ocular administration | Monitor INR closely and adjust dosage, monitoring of INR during ocular administration is advisable |
Roxithromycin | ↑ INR Moderate to severe |
Increases the anticoagulation effect of acenocoumarol | Monitor INR closely when starting or stopping therapy, may cause risk of bleeding due to overantico-agulation |
Quinolone antibiotics | ↑ INR Major | Potentiates anticoagulation, high risk of haemorrhage | Monitor INR closely when starting or stopping therapy, bleeding or hemorrhage may occur, empirical reduction of acenocoumarol dose may be needed |
Doxycycline | ↑ INR Major | Potentiates anticoagulation, high risk of haemorrhage | Monitor INR closely when starting or stopping therapy, bleeding or hemorrhage may occur, empirical reduction of acenocoumarol dose may be needed |
Neomycin | ↑ INR Moderate to severe |
Potentiates anticoagulation | Monitor INR closely when starting or stopping therapy, bleeding or hemorrhage may occur, empirical reduction of acenocoumarol dose may be needed |
Tetracycline | ↑ INR Moderate to severe |
Unknown mechanism, possibly potentiates acenocoumarol, reduced availability of Vitamin K | Monitor INR closely when starting or stopping therapy, overanticoagulation may lead to risk of bleeding, monitor dosage, empirical reduction in dosage may be needed in extreme cases |
INH | ↑ INR Moderate to severe |
Monitor INR closely when starting or stopping therapy, overanticoagulation may lead to risk of bleeding, monitor dosage, empirical reduction in dosage may be needed in extreme cases | |
Sulfamethoxazole | ↑ INR Moderate to severe |
Monitor INR closely when starting or stopping therapy, overanticoagulation may lead to risk of bleeding, monitor dosage, empirical reduction in dosage may be needed in extreme cases | |
Levofloxacin | ↑ INR Moderate to severe |
Monitor INR closely when starting or stopping therapy, overanticoagulation may lead to risk of bleeding, monitor dosage, empirical reduction in dosage may be needed in extreme cases | |
Rifampicin | ↓ INR Moderate to severe |
Induction of hepatic metabolism of anticoagulant | Monitor INR closely, requires higher dose of acenocoumarol |
Barbiturates | ↓ INR Moderate | Induction of hepatic metabolism of anticoagulant | Monitor INR closely, requires higher dose of acenocoumarol |
Antifungal Drugs | |||
Thiabendazole | ↑ INR Moderate to severe |
Strong inhibition of CYP2C9 and CYP2C19, delays acenocoumarol metabolism | Monitor INR closely when starting or stopping therapy, empiric reduction in acenocoumarol dose may be needed |
Fluconazole | ↑ INR Moderate to severe |
Effects more pronounced in patients with reduced renal function due to reduced clearance of fluconazole | Monitor INR closely when starting or stopping fluconazole; stop flucanazole therapy if adverse bleeding episodes occur |
Griseofulvin | ↓ INR Moderate to severe |
Reduces the effect of acenocoumarol by decreasing its serum concentration | Monitor INR closely, increase in acenocoumarol dose may be needed |
INR, international normalized ratio.
The use of antiretroviral drugs (ARVs) is a complex problem, especially in patients requiring additional treatment due to the coexisting diseases. The most important problems concern simultaneous application of combined antiretroviral therapy (cART) with tuberculostatics, certain antifungal drugs from azole group, antibiotics (e.g. clarithromycin), statins, type I and II antiarrhythmic agents, benzodiazepine derivatives, as well as the coumarin derivatives and can cause considerable difficulties in establishing any antiretroviral therapy.
A number of limitations arise from interactions related to ARV pharmacokinetic properties, in particular those metabolised by P450 isoenzymes. Acenocoumarol is metabolized mainly by cytochrome P4502C9 (CYP2C9) which leads to its extensive metabolism when combined with ARV leading to subtherapeutic international normalized ratio (INR) values.
Interactions of Acenocoumarol with antiretroviral drugs
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Raltegravir | Stable INR | Integrase inhibitor, No drug interaction | May be considered as an alternative therapy |
Nevirapine | Stable INR | Non-nucleoside reverse transcriptase inhibitor | May be considered as an alternative therapy |
Ritonavir | ↓ INR Major | Acenocoumarol is metabolized mainly by cytochrome P4502C9 (CYP2C9 induction) which leads to its extensive metabolism when combined with ARV leading to subtherapeutic INR values Anticipated onset: 15 days from initiation of therapy | Use with caution, monitor INR more frequently when starting or stopping ritonavir; up to 3-fold increase in acenocoumarol dose documented in case reports |
Lopinavir | ↓ INR Moderate to severe |
Acenocoumarol is metabolized mainly by cytochrome P4502C9 (CYP2C9 induction) which leads to its extensive metabolism when combined with ARV leading to subtherapeutic INR values Anticipated onset: 15 days from initiation of therapy | Monitor INR more frequently when starting or stopping therapy, increase in acenocoumarol dose may be needed |
Nelfinavir | ↓ INR Moderate |
Acenocoumarol is metabolized mainly by cytochrome P4502C9 (CYP2C9 induction) which leads to its extensive metabolism when combined with ARV leading to subtherapeutic INR values Anticipated onset: 15 days from initiation of therapy | Monitor INR more frequently when starting or stopping therapy, increase in acenocoumarol dose may be needed |
Lopinavir/ Ritonavir | ↓ INR Moderate | Acenocoumarol is metabolized mainly by cytochrome P4502C9 (CYP2C9 induction) which leads to its extensive metabolism when combined with ARV leading to subtherapeutic INR values Anticipated onset: 15 days from initiation of therapy | Monitor INR more frequently when starting or stopping lopinavir–ritonavir; at steady-state, induction interaction more likely to prevail, resulting in reduced INR, requiring up to a 2-fold acenocoumarol dose increase |
Efavirenz | ↓ INR Moderate | Inhibits CYP2C9 | Consider empiric increase of acenocoumarol dose; monitor INR more frequently when starting or stopping efavirenz |
Abacavir | Stable INR | Nucleoside reverse transcriptase inhibitor which does not affect the function of the P450 enzyme | In HIV-infected patients administration of acenocoumarol in combination with abacavir is advisable |
Stavudine | Stable INR | No reported interaction | May be considered as an alternative therapy |
Lamivudine | Stable INR | No reported interaction | May be considered as an alternative therapy |
Proton pump inhibitors (PPIs) are frequently associated with vitamin K antagonists (VKAs) as a means to reduce the risk of gastro-intestinal bleeding. PPIs are potent inhibitors of CYP2C19 and hence associated with a warning during prescription along with a VKA in most of the databases used to detect drug-drug interactions.
Considering the contribution of CYP2C19 in the metabolism of R-acenocoumarol (the isomer mainly responsible for the effect of acenocoumarol) and given the short half-life of PPIs (approximately 1 h), it is advisable to prescribe PPIs safely if the drug is not taken at the same time as acenocoumarol.
Interactions of Acenocoumarol with PPIs
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Esomeprazole | ↑ INR Major | Potent inhibitor of CYP2C19, increases serum concentration of VKA | Warning, use with caution, may cause bleeding, monitor INR closely and frequently (twice a week) during administration of therapy |
Omeprazole | ↓ INR Moderate to severe |
Irreversible inhibition of CYP2C19 | Consider reassessment of INR, monitor INR closely and frequently (twice a week) during administration of therapy |
Pantoprazole | ↑ INR Moderate to severe |
Potent inhibitor of CYP2C19 | Consider reassessment of INR, monitor INR closely and frequently (twice a week) during administration of therapy |
INR, international normalized ratio.
Pharmacodynamically, selective serotonin reuptake inhibitors (SSRIs) could interact with acenocoumarol since the release of serotonin by platelets plays an important role in haemostasis. Recent epidemiological data has demonstrated that SSRIs could significantly increase the risk of gastro-intestinal bleeding. According to some studies, the use of SSRIs among the population treated with coumarins seems to place patients at an increased risk of bleeding. A warning should be added to make the physician aware of this interaction. In contrast to this, serotonin-norepinephrine reuptake inhibitors (SNRIs) cause a decrease in international normalized ratio (INR).
Interactions of Acenocoumarol with Anti-depressants
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
SNRIs | |||
Duloxetine | ↓ INR Moderate to severe |
Induces metabolism of aceconoumerol, causes rapid clearance of the anticoagulant | Monitor closely during initiations and withdrawal of therapy, administer with caution, low dose-short term use is advisable |
Escitalopram | ↑ INR Moderate to severe |
Inhibit the P540 cytochromes and potentiate the anticoagulant effect of Acenocoumarol | Monitor closely during initiations and withdrawal of therapy, administer with caution, low dose-short term use is advisable |
Fluvoxamine | ↑ INR Moderate to severe |
Inhibit the P540 cytochromes and potentiate the anticoagulant effect of Acenocoumarol | Monitor closely during initiations and withdrawal of therapy, administer with caution, low dose-short term use is advisable |
Cetalopram | ↑ INR Moderate to severe |
Inhibit the P540 cytochromes and potentiate the anticoagulant effect of Acenocoumarol | Monitor closely during initiations and withdrawal of therapy, administer with caution, low dose-short term use is advisable |
Paroxetine | ↑ INR Moderate to severe |
Inhibit the P540 cytochromes and potentiate the anticoagulant effect of Acenocoumarol | Monitor closely during initiations and withdrawal of therapy, administer with caution, low dose-short term use is advisable |
Fluoxetine | ↑ INR Moderate to severe |
Inhibit the P540 cytochromes and potentiate the anticoagulant effect of Acenocoumarol | Monitor closely during initiations and withdrawal of therapy, administer with caution, low dose-short term use is advisable |
NSAIDs are reported to increase the risk of bleeding in coumarin users. The mechanism underlying this risk is inhibition of platelet aggregation, however a pharmacokinetic mechanism results in an increased international normalized ratio (INR).
Drug-drug interactions between nonsteroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, and oral anticoagulants are clearly documented in the literature and are frequently highlighted in studies on interactions with oral anticoagulants.
Interactions of Acenocoumarol with Non-steroidal anti-inflammatory drugs
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Ibuprofen | ↑ INR Moderate to severe |
Inhibition of platelet aggregation and production of gastroprotective prostaglandins, high risk of bleeding | Monitor closely for bleeding (especially gastro-intestinal); avoid or minimize concurrent use |
Naproxen | ↑ INR Major | Inhibition of platelet aggregation and production of gastroprotective prostaglandins, high risk of bleeding | Monitor closely for bleeding (especially gastro-intestinal); avoid or minimize concurrent use |
COX-2 Inhibitor (Celecoxib) | ↑ INR Major | Potentiates anticoagulation, alters homeostasis and increase risk of haemorrhage | Use with caution, monitor INR closely and more frequently (twice weekly), this combination is not recommended |
Diclofenac | ↑ INR Moderate to severe |
Risk of gastrointestinal bleeding | Monitor INR closely during therapy, patient may be monitored for gastrointestinal bleeding, reduction in acenocoumarol dose may be needed |
Piroxicam | ↑ INR Moderate to severe |
Risk of gastrointestinal bleeding | Monitor INR closely during therapy, patient may be monitored for gastrointestinal bleeding, reduction in acenocoumarol dose may be needed |
Nabumatone | Stable INR | No reported interaction | Safe, may be considered as an alternative therapy |
In most cases Paracetamol is the analgesic of choice for patients using oral anticoagulants because this drug is justifiably considered to be safer than NSAIDs. However, data suggests that paracetamol clinically interacts with acenocoumarol and is associated with a supratherapeutic INR. Administration of paracetamol at higher doses and/or for longer duration may develop a greater risk for experiencing clinically significant interactions. Given that paracetamol is the analgesic of choice during vitamin K antagonists treatment and based on data reported in the literature data, this association should be represented by a warning only with paracetamol doses of >2 g/day.
Corticosteroids have also been reported to diminish the anticoagulant effect of coumarin derivatives. In case of acenocoumarol, fluctuations in international normalized ratio (INR) may be observed.
Interactions of Acenocoumarol with corticosteroids
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Prednisone | ↓ or ↑ INR Moderate to severe |
Unknown mechanism, possibly due to inhibition of one cytochrome P450 isoenzyme, mostly decreases the anticoagulant effect Anticipated onset: 3 – 10 days from initiation of therapy | Monitor INR closely, consider reassessment of INR every week, increase or decrease in acenocoumarol dose may be needed |
Methylpredni-solone | ↓ or ↑ INR Moderate to severe |
Unknown mechanism, possibly due to inhibition of one cytochrome P450 isoenzyme, mostly decreases the anticoagulant effect Anticipated onset: 3 – 10 days from initiation of therapy | Monitor INR closely, consider reassessment of INR every week, increase or decrease in acenocoumarol dose may be needed |
The anticoagulant effects of acenocoumarol may be enhanced when co-administered with other anticoagulants. This may cause severe increase an international normalized ratio (INR) values and lead to bleeding.
Interactions of Acenocoumarol with Anticoagulants and Antiplatelet drugs
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Anticoagulants | |||
Apixaban | ↑ INR Moderate to severe |
High risk of bleeding | Monitor INR closely and frequently, may cause bleeding, consider prescription of lower doses of Apixaban |
Heparin | ↑ INR Major | Potentiates anticoagulation, alters homeostasis and increases risk of haemorrhage | Use with caution, monitor INR closely and frequently (twice weekly) when starting or stopping Heparin, causes bleeding, combination is not advisable |
Warfarin | ↑ INR Major | Potentiates anticoagulation, high risk of bleeding | Monitor INR closely and frequently, prescribe lowest dose, monitor for bleeding |
Phenprocoumon | ↑ INR Moderate to severe |
High risk of bleeding | Monitor INR closely and frequently, prescribe lowest dose, monitor for bleeding |
Dabigatran | ↑ INR Moderate to severe |
High risk of bleeding | Monitor INR closely and frequently, prescribe lowest dose, monitor for bleeding |
Rivaroxaban | ↑ INR Moderate to severe |
High risk of bleeding | Monitor INR closely and frequently, prescribe lowest dose, monitor for bleeding |
Antiplatelet drugs | |||
Clopidogrel | ↑ INR Moderate to severe |
Inhibits CYP2C9 and has an antiaggregant effect, increased risk of bleeding | Monitor INR closely and frequently, monitor for bleeding, consider prescription of lower doses of clopidogrel, stop therapy in case of adverse events |
Aspirin | ↑ INR Major | Irreversible inhibition of platelet function, increased risk of bleeding Anticipated onset: 1-3 days | Use with caution, use lowest enteric dose (<6 g/d), monitor for bleeding, enteric coated formulations preferred, stop therapy in case of adverse events |
The interaction between antiplatelet drugs and acenocoumarol is important and can be considered as clinically significant through a pharmacokinetic and pharmacodynamic mechanism.
Contraceptives often diminish the anticoagulant effect of vitamin K antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. When possible, concomitant hormonal contraceptives and coumarin derivatives should be avoided in order to eliminate the risk of thromboembolic disorders. Consider using an alternative, nonhormonal contraceptive.
Interactions of Acenocoumarol with Hormones and oral contraceptives
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
Testosterone | ↑ INR Moderate | Increases effectiveness of acenocoumarol | Monitor INR closely during initiation and withdrawal of therapy, decrease in testosterone dose may be needed |
Thyroid hormones | ↑ INR Moderate | Potentiates anticoagulation, increases catabolism of Vitamin K dependent clotting factors | Monitor INR closely and adjust dosage, decrease in acenocoumarol dose may be needed |
Estrogen | ↓ INR Major | Increased hepatic synthesis of procoagulant factors, high risk of thrombosis | Monitor INR closely during initiation and withdrawal of therapy, contraindicated during pregnancy |
Progestin | ↓ INR Moderate | Increases effectiveness of acenocoumarol | Monitor INR closely during initiation and withdrawal of therapy, contraindicated during pregnancy |
Estrogen and Progestin | ↓ INR Moderate to severe |
Increased hepatic synthesis of procoagulant factors by estrogen, risk of thrombosis | Monitor INR closely during initiation and withdrawal of therapy, contraindicated during pregnancy |
INR, international normalized ratio.
Caumarin derivatives can interact with many OTC (over-the-counter, non-prescription), and herbal medications which could increase the risk of either bleeding or clotting. While most of the frequently prescribed medications for cough, cold, allergy, diarrhea etc. are comparatively safer for administration during simultaneous acenocoumarol therapy, several others may have more than one ingredient for pain relief or fever reduction and hence should be taken with caution.
Interactions of Acenocoumarol with most commonly used drugs
Drug | Effect on INR (severity) | Mechanism | Suggested management |
---|---|---|---|
GOUT and Peptic Ulcers Drugs | |||
Colchicine | ↑ INR Moderate | Decreases metabolism of acenocoumarol | Monitor INR to avoid bleeding episodes |
Cimetidine | ↑ INR Moderate | Causes severe diarrhea | If patient is experiencing significant diarrhea with colchicine (>3–4 loose stools per day), check INR; decrease in acenocoumarol dose may be needed |
Anti-cough and cold drugs | |||
Nasal Decongestants (Oxymetazoline, Phenylephrine nasal, Pseudoe-phedrine) |
No published reports | - | May be considered safe for administration |
Anti-cough medications (Dextrome-thorphan, Guaifenesin) |
No published reports | - | May be considered safe for administration |
Antihistamines (Loratadine, Cetirizine) |
No published reports | - | May be considered safe for administration |
Antidiarrheal drugs | |||
Bismuthsubsalicylate | ↑ INR Moderate to severe |
Accentuates the effects of acenocoumarol and leads to excessive bleeding | Avoid drug if possible, may cause bleeding, monitor INR during therapy |
INR, international normalized ratio.
Indications and advisable drug combinations with acenocoumarol therapy
In spite of reported interactions in a few clinical studies, some drugs may still be used in combination with acenocoumarol, although with precaution and regular international normalized ratio (INR) monitoring. These drugs may exhibit lesser severity of interaction when administered along with acenocoumarol and hence can be considered as an alternative therapy.
Indication | Advisable combination therapy (with close INR monitoring) |
---|---|
Atrial fibrillation/stenosis/stroke35 | Triflusal (fewer bleeding episodes reported, safer than aspirin) |
High cholesterol24 | Atorvastatin |
Pain relief30 | Nabumetone, Paracetamol (at extremely low doses and short time) |
Headache, fever | Acetamenophen (Not more than 4 g/d) |
Sinus and nasal congestion36 | Pseudoephedrine, Phenylephrine Oxymetazoline Nose Sprays (Limit use to no more than 3-5 days) |
Cough36 | Guaifenesin, Dextromethorphan |
Allergy like symptoms36 | Loratadine, Cetirizine |
Diabetes22 | Nateglinide |
Pulmonary Arterial Hypertension | Sitaxentan |
Depression37 | Nortriptyline, Mirtazapine, Paroxetine |
Retroviral infection | Abacavir, Nevirapine, Lamivudine |
Diarrhoea38 | Loperamide, Atropine |